Bottom Line:
IL-1 receptor accessory protein-like 1 (IL1RAPL1) is responsible for nonsyndromic intellectual disability and is associated with autism.Furthermore, the behavioural flexibility was slightly reduced in the T-maze test.These results suggest that IL1RAPL1 ablation resulted in spine density decrease and affected not only learning but also behavioural flexibility, locomotor activity and anxiety.

Affiliation: 1] Department of Molecular Neurobiology and Pharmacology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan [2] Liaison Academy, School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.

ABSTRACTIL-1 receptor accessory protein-like 1 (IL1RAPL1) is responsible for nonsyndromic intellectual disability and is associated with autism. IL1RAPL1 mediates excitatory synapse formation through trans-synaptic interaction with PTPδ. Here, we showed that the spine density of cortical neurons was significantly reduced in IL1RAPL1 knockout mice. The spatial reference and working memories and remote fear memory were mildly impaired in IL1RAPL1 knockout mice. Furthermore, the behavioural flexibility was slightly reduced in the T-maze test. Interestingly, the performance of IL1RAPL1 knockout mice in the rotarod test was significantly better than that of wild-type mice. Moreover, IL1RAPL1 knockout mice consistently exhibited high locomotor activity in all the tasks examined. In addition, open-space and height anxiety-like behaviours were decreased in IL1RAPL1 knockout mice. These results suggest that IL1RAPL1 ablation resulted in spine density decrease and affected not only learning but also behavioural flexibility, locomotor activity and anxiety.

Mentions:
We generated IL1RAPL1 knockout mice using C57BL/6 embryonic stem cells24 (see Supplementary Fig. S1 online). The IL1RAPL1 knockout mice grew and mated normally. Western blot analysis confirmed the absence of IL1RAPL1 of ~85 kDa in the brain of the mutant mice (Fig. 1A). The size and proportion of the brain and the Nissl-staining patterns of the cerebral cortex and hippocampus of the mutant mice were comparable to those of the wild-type mice in agreement with a previous report25 (Fig. 1B and C).

Mentions:
We generated IL1RAPL1 knockout mice using C57BL/6 embryonic stem cells24 (see Supplementary Fig. S1 online). The IL1RAPL1 knockout mice grew and mated normally. Western blot analysis confirmed the absence of IL1RAPL1 of ~85 kDa in the brain of the mutant mice (Fig. 1A). The size and proportion of the brain and the Nissl-staining patterns of the cerebral cortex and hippocampus of the mutant mice were comparable to those of the wild-type mice in agreement with a previous report25 (Fig. 1B and C).

Bottom Line:
IL-1 receptor accessory protein-like 1 (IL1RAPL1) is responsible for nonsyndromic intellectual disability and is associated with autism.Furthermore, the behavioural flexibility was slightly reduced in the T-maze test.These results suggest that IL1RAPL1 ablation resulted in spine density decrease and affected not only learning but also behavioural flexibility, locomotor activity and anxiety.

Affiliation:
1] Department of Molecular Neurobiology and Pharmacology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan [2] Liaison Academy, School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.

ABSTRACTIL-1 receptor accessory protein-like 1 (IL1RAPL1) is responsible for nonsyndromic intellectual disability and is associated with autism. IL1RAPL1 mediates excitatory synapse formation through trans-synaptic interaction with PTPδ. Here, we showed that the spine density of cortical neurons was significantly reduced in IL1RAPL1 knockout mice. The spatial reference and working memories and remote fear memory were mildly impaired in IL1RAPL1 knockout mice. Furthermore, the behavioural flexibility was slightly reduced in the T-maze test. Interestingly, the performance of IL1RAPL1 knockout mice in the rotarod test was significantly better than that of wild-type mice. Moreover, IL1RAPL1 knockout mice consistently exhibited high locomotor activity in all the tasks examined. In addition, open-space and height anxiety-like behaviours were decreased in IL1RAPL1 knockout mice. These results suggest that IL1RAPL1 ablation resulted in spine density decrease and affected not only learning but also behavioural flexibility, locomotor activity and anxiety.